201 research outputs found
Austin also must be remembered. The Augustinian legacy in Milton's work
Full text linkWhen I started working on this project, with a limited knowledge of Augustine, but determined to spot his presence in Miltonâs poetry, I was little aware of the intricacy of the relationship between the two authors. At this stage of my research, I do subscribe to Savoyeâs opinion, that this relationship is pervasive. However, one could safely add, it is as pervasive as it is hidden, primarily because of changed cultural paradigms, so that Miltonâs references are no longer familiar to the reader.
As I have pointed out in my presentation of the state of the art, these articulations are hardly made explicit in Miltonâs Oeuvre and also in critical literature they are hardly brought to the surface. My objective has been to make them a little more visible.
I have started my own process of discovery from the works where Milton more openly (but not completely) acknowledges his Augustinian sources, although arguably mediated. As concerns Samson Agonistes, I have presented a reading through Augustinian lenses. I am by no means claiming that mine is the best of all possible readings, but through those lenses I have been able to see a coherence, in Miltonâs dramatic poem, that is not generally recognized.
On the other hand, I thoroughly agree that âone cannot simply take any English poet and turn the post-structuralist critical machine loose on him or her in good faithâ. In particular, I am aware that I have read Miltonâs works against the current critical grain which, with a powerful turn impressed by Empsonâs Miltonâs God, is continually surfacing Miltonâs idiosyncrasies in order to cancel the received picture of a Christian author. Rather, I agree with Cirillo that Miltonâs perspective is that of âa professed Christian poet whose Christian consciousness, no matter how heterodox, colored virtually everything he wrote.â.We may ask, echoing Febvre on Rabelais, âMais de quel christianisme? In accordance with very traditional, even traditionalist Milton Criticism, I think it can safely be stated that Milton is a post-Reformation religious author, and one whose endeavour to âjustify the ways of God to menâ had to come to terms with the difficult task to find signs of providential history in the aftermath of a civil war and in the adverse context of the Restoration. His last published poems deal with this problem in different terms. As readers, we can come to different conclusions as to the texts. Behind them there is the man, âest abyssus humanae conscientiae,â in front of which, after Augustine, I can only say: "nescio"
Hope and Despair in Milton's Samson Agonistes and Paradise Regained
No full textHope and Despair in Milton’s Samson
Agonistes and Paradise Regained
Abstract
This thesis aims to explore the notions of hope and despair in Milton’s companion poems, Paradise Regained and Samson Agonistes. In the first chapter, I will define and establish the notions of hope and despair in the Christian context by examining the configurations of these two ideas in the Bible, fathers of the church, and representative reformation theologians. A broader contextual study will include renaissance poets and prose writers and one emblem author. The second chapter presents an outline and discussion of the critical history of these two poems, and I will focus upon critics’ reading of hope and despair in these two poems. The third and fourth chapters are devoted to Samson Agonistes and Paradise Regained respectively. Samson and Christ exemplify true hope. A false hope is then embraced by Samson’s visitors, the Chorus, Manoa, Dalila, and Harapha, and the Philistines, and Jesus’ tempter, Satan. In these two chapters, a revelation of the causal relationship between other virtues, faith, patience, and confidence, and hope will enhance our understanding of Christian hope. Milton’s treatments of hope as an act and a tangible being can be evidenced in the protagonists of his two major poems. Samson conquers his near-despair, withstands temptations of false hope and despair, and eventually regains hope as God’s chosen. Jesus passes the trials of faith and patience, maturing in self-knowledge, defeating the despairing Devil, and proving himself as Hope of mankind. The epilogue of the thesis is intended to compare Milton’s representations of hope in Samson and Christ.Table of Contents
Page
Acknowledgement iii
Abstract iv
Chapter 1
Introduction: Hope and Despair in the Renaissance and Reformation: a Context...................................1
I. Definitions and Biblical Tradition
II. The Patristic Tradition: St. Augustine and St. Thomas
III. The Renaissance and the Reformation Tradition
Chapter 2
The Critical History of Samson Agonistes and Paradise Regained ............................................... 43
Chapter 3
Reading Samson Agonistes............................ 65
I. Linguistic Distinction: Hope as a Verb
II. Samson Agonistes and the Book of Judges
III. Hope and Faith
IV. Manoa’s False Hope
V. Regaining Hope: Samson Conquering Despair
Chapter 4
Reading Paradise Regained ..........................104
I. Linguistic Definition: Hope as a Noun
II. Mary and the Apostles’ Concepts of Christian Hope
III. Satan’s False Hope and Despair
IV. Hope Confirmed: Christ’s Growth
Epilogue ...............................................140
Works Cited ............................................144
Appendi
Problemes of beautie and all humane affections. VVritten in Italian by Tho: Buoni, cittizen of Lucca. With a discourse of beauty, by the same author. Translated into English, by S.L. Gent [electronic resource]
No full textS.L. = Samson Lennard.A translation of: I problemi della belleza.The last two leaves are blank.A variant of the undated edition.Register begins with B.Folger Library copy identified as 4103a, and Emmanuel College copy as 4103, on UMI microfilms.Reproductions of the originals in the Folger Shakespeare Library and Emmanuel College (University of Cambridge). Library.Appears at reel 646 (Folger Shakespeare Library copy) and at reel 657 (Emmanuel College (University of Cambridge). Library copy).STC (2nd ed.)Electronic reproduction
Eine dreidimensionale Sicht auf die Grenzfläche zwischen Kernhülle und Chromatin
No full textThe nucleus is an organelle characteristic of eukaryotic cells and its
mechanical properties play an essential role in the behavior of the cell, in
particular its motility, polarity and survival. It is surrounded by an
envelope comprising an inner membrane and an outer membrane, as well as a
large number of proteins. These proteins are either anchored at the nuclear
membrane, as emerin, or form a filament meshwork lining the inner nuclear
membrane, as lamins. My thesis objectives were to understand molecular
mechanisms deficient in two types of genetic diseases caused by mutations in
inner nuclear envelope proteins: Emery-Dreifuss muscular dystrophy, associated
to mutations in emerin and A-type lamins, and progeroid syndromes caused by
mutations in A-type lamins. First, we showed that the emerin protein self-
assembles in vitro and in cells (Herrada, Samson et al., ACS Chem. Biol.,
2015). I then studied the structure of emerin oligomers, determined the
minimal protein fragment necessary for the formation of these oligomers,
identify residues forming the structural core of these oligomers by solid-
state NMR in collaboration with the group of Prof A. Lange (FMP Berlin). And
described the impact of emerin mutations causing Emery-Dreifuss muscular
dystrophy on emerin self-assembly (Samson et al., Biomol. NMR Assign. 2016,
Samson et al., FEBS J. 2017). Then, I observed, mainly using solution-state
NMR, that only the self-assembled form of emerin is able to interact with
A-type lamin tail, and that mutants causing Emery-Dreifuss muscular dystrophy
and unable to self-assemble are also defective in A-type lamin binding. I also
obtained preliminary data showing that phosphorylation of emerin by the Src
kinase, observed after a mechanical stress in purified nuclei, regulates the
interaction between self-assembled emerin and A-type lamins. Finally, I showed
that the monomeric form of emerin is able to form a ternary complex with
A-type lamin tail through the chromatin-associated protein Barrier-to-
Autointegration Factor (BAF). After having measured the protein-protein
affinities within this complex, identified the minimal protein fragments
involved in the complex and developed a robust protocol for purification of
this complex, I was able to obtain crystals under several conditions.
Subsequently, I solved the 3D structure of this complex by molecular
replacement at a resolution of 2 Å. Finally, I showed that mutations in A-type
lamins causing autosomal recessive progeroid syndromes impair interaction with
BAF in vitro, and our collaborators at Univ. Paris Diderot, the team of Dr B.
Buendia, showed that these same mutations induce a significant decrease in the
proximity between lamin A and BAF in HeLa cells. An article with me as a first
author is in preparation that reports all these new data.Der Zellkern ist eine charakteristische Organelle einer eukaryotischen Zelle.
Seine mechanischen Eigenschaften spielen eine wesentliche Rolle für das
Verhalten der Zelle, insbesondere für deren Beweglichkeit, Polarität und
Überleben. Es ist von einer Hülle umgeben, die eine innere Membran und eine
äußere Membran sowie eine große Anzahl von Proteinen umfasst. Diese Proteine
sind entweder an der Kernmembran verankert, als Emerin, oder bilden ein
Filamentnetz, das die innere Kernmembran auskleidet, als Lamine. Ziel meiner
Doktorarbeit war, molekulare Mechanismen zu verstehen, die bei zwei Arten
genetischer Erkrankungen, die durch Mutationen in inneren Kernhüllproteinen
verursacht werden, fehlen: Emery-Dreifuss-Muskeldystrophie, assoziiert mit
Mutationen in Emerin- und A-Laminen, und Progeroid-Syndrome durch Mutationen
in A- Laminen ein. Zunächst zeigten wir, dass das Emerin-Protein in vitro und
in Zellen selbstorganisiert ist (Herada, Samson et al., ACS Chem. Biol.,
2015). Ich untersuchte dann die Struktur von Emerin-Oligomeren, bestimmte das
minimale Proteinfragment, das für die Bildung dieser Oligomere notwendig ist,
identifiziere Reste, die den strukturellen Kern dieser Oligomere bilden, durch
Festkörper-NMR in Zusammenarbeit mit der Gruppe von Prof. A. Lange (FMP
Berlin) und beschrieb den Einfluss von Emerin-Mutationen, die Emery-Dreifuss-
Muskeldystrophie auf die emerierende Selbstorganisation verursachen (Samson et
al., Biomol. NMR Assign. 2016, Samson et al., FEBS J. 2017). Dann beobachtete
ich, hauptsächlich unter Verwendung von Lösungs-NMR, dass nur die
selbstorganisierte Form von Emerin in der Lage ist, mit dem A-Typ-Lamin-
Schwanz zu interagieren, und dass Mutanten, die Emery-Dreifuss-
Muskeldystrophie verursachen und nicht in der Lage sind, sich selbst zu
assemblieren in A-Laminen. Ich erhielt auch vorläufige Daten, die zeigen, dass
die Phosphorylierung von Emerin durch die Src-Kinase, die nach einer
mechanischen Belastung in gereinigten Kernen beobachtet wird, die
Wechselwirkung zwischen selbstorganisierten Emerin- und A-Typ-Laminen
reguliert. Schließlich zeigte ich, dass die monomere Form von Emerin einen
ternären Komplex mit dem A-Typ-Lamin-Tail durch das Chromatin-assoziierte
Protein Barrier-to-Autointegration Factor (BAF) bilden kann. Nachdem ich die
Protein-Protein-Affinitäten in diesem Komplex gemessen, die minimalen
Proteinfragmente identifiziert und ein robustes Protokoll für die Reinigung
dieses Komplexes entwickelt hatte, konnte ich Kristalle unter verschiedenen
Bedingungen erhalten. Anschließend löste ich die 3D-Struktur dieses Komplexes
durch molekularen Ersatz mit einer Auflösung von 2 Å. Schließlich zeigte ich,
dass Mutationen in A-Laminen, die autosomal-rezessive Progeroid-Syndrome
verursachen, die Interaktion mit BAF in vitro beeinträchtigen, und unsere
Mitarbeiter von Univ. Paris Diderot, das Team von Dr. B. Buendia, zeigte, dass
diese gleichen Mutationen eine signifikante Abnahme der Nähe zwischen Lamin A
und BAF in HeLa-Zellen induzieren. Ein Artikel mit mir als Erstautor ist in
Vorbereitung, der all diese neuen Daten berichtet
Review of Robert Stefanotti, O.Carm, \u3ci\u3eThe Phoenix of Rennes; the Life and Poetry of John of St. Samson 1571-1636\u3c/i\u3e
Full text linkThis monograph deals with the life and work of John of St. Samson. lay brother of the Carmelite Ancient Observance, reformer, mystic. author of spiritual treatises and poet. Curiously, this blind prolific Counter-Reformation era author is little known today even by his compatriots and is virtually unknown outside the French-speaking world.
In his analysis of the formal elements of Jean\u27s work, Stefanotti stresses the mystic\u27s preference for classical structures: in poetry, the sonnet; in music, the chanson. Among figures of speech, Jean was fond of coupling, tripling, oxymoron, often employed to express paradox (p. 66, 70). The author points to the frequent compact, polisemic employment of cornerstone terms and alludes to the conflation of symbols, which allows us to view Jean\u27s poetic texts as specifically mystical ones (p. 111). In the chapter dedicated to spiritual images, Stefanotti accentuates the influence of the Rheno-Flemish school of mysticism upon Jean du Moulin. With its roots geographically to the North, this late medieval school is characterized by a strong Trinitarian element, by the doctrine of exemplarism, and an emphasis on the notion of the image of God being impressed in the souL Jean\u27s spiritual theology and his poetic imagery are indeed permeated by the Rheno-Flemish John Ruusbroec, as the research of P. W.Janssen has highlighted. Thus Stefanotti summarizes: John of St. Samson used the tools of Baroque poetry, Ruusbroecian spirituality and the lived life of Carmel to craft his spiritual texts (p. 129)
Une représentation en trois dimensions de l'interface entre l'enveloppe nucléaire et la chromatine
No full textThe nucleus is an organelle characteristic of eukaryotic cells and its mechanical properties play an essential role in the behavior of the cell, in particular its motility, polarity and survival. It is surrounded by an envelope comprising an inner membrane and an outer membrane, as well as a large number of proteins. These proteins are either anchored at the nuclear membrane, as emerin, or form a filament meshwork lining the inner nuclear membrane, as lamins. My thesis objectives were to understand molecular mechanisms deficient in two types of genetic diseases caused by mutations in inner nuclear envelope proteins: Emery-Dreifuss muscular dystrophy, associated to mutations in emerin and A-type lamins, and progeroid syndromes caused by mutations in A-type lamins.First, we showed that the emerin protein self-assembles in vitro and in cells (Herrada, Samson et al., ACS Chem. Biol., 2015). I then studied the structure of emerin oligomers, determined the minimal protein fragment necessary for the formation of these oligomers, identify residues forming the structural core of these oligomers by solid-state NMR in collaboration with the group of Prof A. Lange (FMP Berlin), and described the impact of emerin mutations causing Emery-Dreifuss muscular dystrophy on emerin self-assembly (Samson et al., Biomol. NMR Assign. 2016, Samson et al., FEBS J. 2017). Then, I observed, mainly using solution-state NMR, that only the self-assembled form of emerin is able to interact with A-type lamin tail, and that mutants causing Emery-Dreifuss muscular dystrophy and unable to self-assemble are also defective in A-type lamin binding. I also obtained preliminary data showing that phosphorylation of emerin by the Src kinase, observed after a mechanical stress in purified nuclei, regulates the interaction between self-assembled emerin and A-type lamins.Finally, I showed that the monomeric form of emerin is able to form a ternary complex with A-type lamin tail through the chromatin-associated protein Barrier-to-Autointegration Factor (BAF). After having measured the protein-protein affinities within this complex, identified the minimal protein fragments involved in the complex and developed a robust protocol for purification of this complex, I was able to obtain crystals under several conditions. Subsequently, I solved the 3D structure of this complex by molecular replacement at a resolution of 2 Å. Finally, I showed that mutations in A-type lamins causing autosomal recessive progeroid syndromes impair interaction with BAF in vitro, and our collaborators at Univ. Paris Diderot, the team of Dr B. Buendia, showed that these same mutations induce a significant decrease in the proximity between lamin A and BAF in HeLa cells. An article with me as a first author is in preparation that reports all these new data.Le noyau est un organite caractéristique des cellules eucaryotes et les propriétés mécaniques de ce dernier jouent un rôle essentiel dans le comportement de la cellule, notamment sa motilité, sa polarité et sa survie. Le noyau est entouré par une enveloppe comprenant une membrane interne et une membrane externe, ainsi que de nombreuses protéines. Mes objectifs de thèse étaient de comprendre des mécanismes moléculaires déficients dans deux types de maladies génétiques causées par des mutations dans les lamines: la dystrophie musculaire d’Emery-Dreifuss et les syndromes de type progéroïde.Dans un premier temps, nous avons montré que l’émerine s’auto-associe in vitro et en cellules (Herrada et al. ACS Chem. Biol. 2015). J’ai ensuite étudié la structure des oligomères d’émerine, déterminé le fragment protéique minimal nécessaire à la formation de ces oligomères et décrit l’impact de mutations de l’émerine, causant une dystrophie musculaire d’Emery-Dreifuss, sur son auto-assemblage (Samson et al. Biomol NMR Assign. 2016 ; Samson et al. FEBS J. 2016). Puis, j’ai montré que seule cette forme auto-assemblée de l’émerine est capable d’interagir avec la lamine A et que la phosphorylation de l’émerine par la kinase Src, observée suite à un stress mécanique, régule cette interaction entre l’enveloppe nucléaire et le nucléosquelette.Pour finir, j’ai montré que la forme monomérique de l’émerine est capable de former un complexe ternaire avec BAF et la lamine A. Après avoir mesuré les affinités protéine-protéine au sein de ce complexe, identifié les fragments minimaux des différentes protéines permettant de former ce complexe et mis au point un protocole robuste de purification de ce complexe, j’ai pu obtenir des cristaux de ce complexe dans plusieurs conditions. Par la suite, nous avons pu résoudre la structure de ce complexe par remplacement moléculaire avec une résolution de 2 Å. Enfin, j'ai montré que les mutations dans les lamines de type A provoquant des syndromes de type progéroïde pouvaient altérer l'interaction avec BAF in vitro, et nos collaborateurs, l'équipe du Dr B. Buendia (Paris Diderot), ont montré que ces mêmes mutations induisaient une diminution significative de la proximité entre la lamine A et BAF dans les cellules HeLa. Un article, où je suis premier auteur, vient d’être soumis au journal NSMB
Une représentation en trois dimensions de l'interface entre l'enveloppe nucléaire et la chromatine
Full text linkThe nucleus is an organelle characteristic of eukaryotic cells and its mechanical properties play an essential role in the behavior of the cell, in particular its motility, polarity and survival. It is surrounded by an envelope comprising an inner membrane and an outer membrane, as well as a large number of proteins. These proteins are either anchored at the nuclear membrane, as emerin, or form a filament meshwork lining the inner nuclear membrane, as lamins. My thesis objectives were to understand molecular mechanisms deficient in two types of genetic diseases caused by mutations in inner nuclear envelope proteins: Emery-Dreifuss muscular dystrophy, associated to mutations in emerin and A-type lamins, and progeroid syndromes caused by mutations in A-type lamins.First, we showed that the emerin protein self-assembles in vitro and in cells (Herrada, Samson et al., ACS Chem. Biol., 2015). I then studied the structure of emerin oligomers, determined the minimal protein fragment necessary for the formation of these oligomers, identify residues forming the structural core of these oligomers by solid-state NMR in collaboration with the group of Prof A. Lange (FMP Berlin), and described the impact of emerin mutations causing Emery-Dreifuss muscular dystrophy on emerin self-assembly (Samson et al., Biomol. NMR Assign. 2016, Samson et al., FEBS J. 2017). Then, I observed, mainly using solution-state NMR, that only the self-assembled form of emerin is able to interact with A-type lamin tail, and that mutants causing Emery-Dreifuss muscular dystrophy and unable to self-assemble are also defective in A-type lamin binding. I also obtained preliminary data showing that phosphorylation of emerin by the Src kinase, observed after a mechanical stress in purified nuclei, regulates the interaction between self-assembled emerin and A-type lamins.Finally, I showed that the monomeric form of emerin is able to form a ternary complex with A-type lamin tail through the chromatin-associated protein Barrier-to-Autointegration Factor (BAF). After having measured the protein-protein affinities within this complex, identified the minimal protein fragments involved in the complex and developed a robust protocol for purification of this complex, I was able to obtain crystals under several conditions. Subsequently, I solved the 3D structure of this complex by molecular replacement at a resolution of 2 Å. Finally, I showed that mutations in A-type lamins causing autosomal recessive progeroid syndromes impair interaction with BAF in vitro, and our collaborators at Univ. Paris Diderot, the team of Dr B. Buendia, showed that these same mutations induce a significant decrease in the proximity between lamin A and BAF in HeLa cells. An article with me as a first author is in preparation that reports all these new data.Le noyau est un organite caractéristique des cellules eucaryotes et les propriétés mécaniques de ce dernier jouent un rôle essentiel dans le comportement de la cellule, notamment sa motilité, sa polarité et sa survie. Le noyau est entouré par une enveloppe comprenant une membrane interne et une membrane externe, ainsi que de nombreuses protéines. Mes objectifs de thèse étaient de comprendre des mécanismes moléculaires déficients dans deux types de maladies génétiques causées par des mutations dans les lamines: la dystrophie musculaire d’Emery-Dreifuss et les syndromes de type progéroïde.Dans un premier temps, nous avons montré que l’émerine s’auto-associe in vitro et en cellules (Herrada et al. ACS Chem. Biol. 2015). J’ai ensuite étudié la structure des oligomères d’émerine, déterminé le fragment protéique minimal nécessaire à la formation de ces oligomères et décrit l’impact de mutations de l’émerine, causant une dystrophie musculaire d’Emery-Dreifuss, sur son auto-assemblage (Samson et al. Biomol NMR Assign. 2016 ; Samson et al. FEBS J. 2016). Puis, j’ai montré que seule cette forme auto-assemblée de l’émerine est capable d’interagir avec la lamine A et que la phosphorylation de l’émerine par la kinase Src, observée suite à un stress mécanique, régule cette interaction entre l’enveloppe nucléaire et le nucléosquelette.Pour finir, j’ai montré que la forme monomérique de l’émerine est capable de former un complexe ternaire avec BAF et la lamine A. Après avoir mesuré les affinités protéine-protéine au sein de ce complexe, identifié les fragments minimaux des différentes protéines permettant de former ce complexe et mis au point un protocole robuste de purification de ce complexe, j’ai pu obtenir des cristaux de ce complexe dans plusieurs conditions. Par la suite, nous avons pu résoudre la structure de ce complexe par remplacement moléculaire avec une résolution de 2 Å. Enfin, j'ai montré que les mutations dans les lamines de type A provoquant des syndromes de type progéroïde pouvaient altérer l'interaction avec BAF in vitro, et nos collaborateurs, l'équipe du Dr B. Buendia (Paris Diderot), ont montré que ces mêmes mutations induisaient une diminution significative de la proximité entre la lamine A et BAF dans les cellules HeLa. Un article, où je suis premier auteur, vient d’être soumis au journal NSMB
A three-dimensional view of the interface between nuclear envelope and chromatin
No full textLe noyau est un organite caractéristique des cellules eucaryotes et les propriétés mécaniques de ce dernier jouent un rôle essentiel dans le comportement de la cellule, notamment sa motilité, sa polarité et sa survie. Le noyau est entouré par une enveloppe comprenant une membrane interne et une membrane externe, ainsi que de nombreuses protéines. Mes objectifs de thèse étaient de comprendre des mécanismes moléculaires déficients dans deux types de maladies génétiques causées par des mutations dans les lamines: la dystrophie musculaire d’Emery-Dreifuss et les syndromes de type progéroïde.Dans un premier temps, nous avons montré que l’émerine s’auto-associe in vitro et en cellules (Herrada et al. ACS Chem. Biol. 2015). J’ai ensuite étudié la structure des oligomères d’émerine, déterminé le fragment protéique minimal nécessaire à la formation de ces oligomères et décrit l’impact de mutations de l’émerine, causant une dystrophie musculaire d’Emery-Dreifuss, sur son auto-assemblage (Samson et al. Biomol NMR Assign. 2016 ; Samson et al. FEBS J. 2016). Puis, j’ai montré que seule cette forme auto-assemblée de l’émerine est capable d’interagir avec la lamine A et que la phosphorylation de l’émerine par la kinase Src, observée suite à un stress mécanique, régule cette interaction entre l’enveloppe nucléaire et le nucléosquelette.Pour finir, j’ai montré que la forme monomérique de l’émerine est capable de former un complexe ternaire avec BAF et la lamine A. Après avoir mesuré les affinités protéine-protéine au sein de ce complexe, identifié les fragments minimaux des différentes protéines permettant de former ce complexe et mis au point un protocole robuste de purification de ce complexe, j’ai pu obtenir des cristaux de ce complexe dans plusieurs conditions. Par la suite, nous avons pu résoudre la structure de ce complexe par remplacement moléculaire avec une résolution de 2 Å. Enfin, j'ai montré que les mutations dans les lamines de type A provoquant des syndromes de type progéroïde pouvaient altérer l'interaction avec BAF in vitro, et nos collaborateurs, l'équipe du Dr B. Buendia (Paris Diderot), ont montré que ces mêmes mutations induisaient une diminution significative de la proximité entre la lamine A et BAF dans les cellules HeLa. Un article, où je suis premier auteur, vient d’être soumis au journal NSMB.The nucleus is an organelle characteristic of eukaryotic cells and its mechanical properties play an essential role in the behavior of the cell, in particular its motility, polarity and survival. It is surrounded by an envelope comprising an inner membrane and an outer membrane, as well as a large number of proteins. These proteins are either anchored at the nuclear membrane, as emerin, or form a filament meshwork lining the inner nuclear membrane, as lamins. My thesis objectives were to understand molecular mechanisms deficient in two types of genetic diseases caused by mutations in inner nuclear envelope proteins: Emery-Dreifuss muscular dystrophy, associated to mutations in emerin and A-type lamins, and progeroid syndromes caused by mutations in A-type lamins.First, we showed that the emerin protein self-assembles in vitro and in cells (Herrada, Samson et al., ACS Chem. Biol., 2015). I then studied the structure of emerin oligomers, determined the minimal protein fragment necessary for the formation of these oligomers, identify residues forming the structural core of these oligomers by solid-state NMR in collaboration with the group of Prof A. Lange (FMP Berlin), and described the impact of emerin mutations causing Emery-Dreifuss muscular dystrophy on emerin self-assembly (Samson et al., Biomol. NMR Assign. 2016, Samson et al., FEBS J. 2017). Then, I observed, mainly using solution-state NMR, that only the self-assembled form of emerin is able to interact with A-type lamin tail, and that mutants causing Emery-Dreifuss muscular dystrophy and unable to self-assemble are also defective in A-type lamin binding. I also obtained preliminary data showing that phosphorylation of emerin by the Src kinase, observed after a mechanical stress in purified nuclei, regulates the interaction between self-assembled emerin and A-type lamins.Finally, I showed that the monomeric form of emerin is able to form a ternary complex with A-type lamin tail through the chromatin-associated protein Barrier-to-Autointegration Factor (BAF). After having measured the protein-protein affinities within this complex, identified the minimal protein fragments involved in the complex and developed a robust protocol for purification of this complex, I was able to obtain crystals under several conditions. Subsequently, I solved the 3D structure of this complex by molecular replacement at a resolution of 2 Å. Finally, I showed that mutations in A-type lamins causing autosomal recessive progeroid syndromes impair interaction with BAF in vitro, and our collaborators at Univ. Paris Diderot, the team of Dr B. Buendia, showed that these same mutations induce a significant decrease in the proximity between lamin A and BAF in HeLa cells. An article with me as a first author is in preparation that reports all these new data
Distill, my beating heart : releasing the "liquid prisoner" of Shakespeare's sonnets ; and, An internal drama : spiritual recovery by trial in John Milton's Samson Agonistes
Full text link"Many of Shakespeare's sonnets refer to fermentation or distillation to explain the effects of aging, and the possibilities for preserving love and beauty. The metaphorical attention that Shakespeare gives to those chemical arts in the Sonnets allows him to develop and express a complex interaction between beauty, love, and the passing of time. In this paper I examine portions of sixteenth-century theoretical and practical texts on the subjects of fermentation and distillation, relating what might have been Shakespeare's understanding of them to lines and sections of his Sonnets where the chemical arts enrich his arguments about love. Samson Agonistes can be understood as an internal monologue Samson performs for himself, and for God. The characters who visit Samson create internal challenges for him that allow him to confront the events of his life and the thoughts that led him to act against God's will. By facing those characters as individual, distinct trials he recovers his spirituality and free will, and only after those achievements regains his physical strength, at which point he can continue to do the work of God."--Abstract from author supplied metadata
The Artist I Want To Be
No full textThis thesis writing is a short personal essay and narrative account of the art, social, and private life of its author. This writing is an attempt to outline the question of what it means to be an American contemporary artist and what it means to want to be an American contemporary artist. This writing is an attempt to outline what is the function or expectation of contemporary art, and what is our desire for it. When I say outline I mean the shadow and not what casts it
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